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PubMed2006

Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome.

OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study. SETTING: Outpatient clinic, at a university hospital in Denmark. PATIENT(S): Thirty obese women with PCOS and 14 weight-matched healthy females. INTERVENTION(S): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME MEASURE(S): Fasting blood samples, 24-hour 20-minute integrated blood sampling (LH, insulin, and C-peptide), euglycemic hyperinsulinemic clamps including 3-(3)H glucose, and indirect calorimetry were performed before and after the intervention period. RESULT(S): Patients with PCOS had significantly lower insulin sensitivity compared with controls, including significantly decreased insulin-stimulated oxidative and nonoxidative glucose metabolism. Pioglitazone treatment resulted in significantly lower levels of fasting insulin and significantly higher insulin sensitivity, increased insulin-stimulated glucose oxidation, and increased insulin-stimulated inhibition of lipid oxidation. During 24-hour blood sampling, significantly lower area under-the-curve insulin and lower median insulin levels were observed. Secretion profiles of LH and E(2) and T levels did not change significantly. CONCLUSION(S): Insulin resistance in PCOS was characterized by hyperinsulinemia, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment.

Adult↗

PubMed2006

Serum sex hormone-binding globulin levels show too much variability to be used effectively as a screening marker for insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the relationship between serum sex hormone-binding globulin (SHBG) and parameters of insulin sensitivity in women with polycystic ovary syndrome (PCOS) and controls, and determine the feasibility of using SHBG levels to predict insulin resistance. DESIGN: Evaluation of a prospectively collected database. SETTING: University reproductive center. PATIENT(S): A total of 21 women with PCOS and 17 controls. INTERVENTION(S): Oral glucose tolerance test. MAIN OUTCOME MEASURE(S): Correlations of serum SHBG and parameters of insulin sensitivity. RESULT(S): [1] Among all participants, SHBG levels indicated a correlation between the fasting glucose-to-insulin (GI) ratio and the quantitative insulin sensitivity check index (QUICKI). Participants with PCOS demonstrated significant correlations of SHBG and fasting GI ratio, 1-hour postglucola insulin levels, and random 17-hydroxyprogesterone (17ohP4) levels. Among controls, SHBG and fasting serum glucose and 2-hour postglucola serum glucose levels were associated. [2] Participants with PCOS and lean controls exhibited different glucose and insulin responses to 75 g of glucose at 1 and 2 hours postchallenge, resulting in paradoxically similar GI ratios. CONCLUSION(S): [1] Although certain parameters of insulin status and serum SHBG demonstrated statistically significant correlation coefficients, these relationships are weak and SHBG cannot be used as a predictor of insulin resistance. [2] The post-glucose load GI ratio cannot be used to determine the magnitude of insulin resistance.

Adult↗

PubMed2006

Plasma adrenomedullin levels in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate adrenomedullin levels in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): Thirty-eight women with PCOS and 29 healthy control subjects were enrolled in the study. INTERVENTION(S): Plasma adrenomedullin, serum androstenedione, free T, T, DHEAS, SHBG, thyrotropin, PRL, FSH, LH, and E2 were measured in each subject. Insulin resistance was estimated by fasting insulin level, fasting glucose:insulin ratio and 75-g glucose tolerance test for 2 hours. MAIN OUTCOME MEASURE(S): Plasma adrenomedullin levels and correlations among adrenomedullin and gonadotropins, female sex steroids, androgens, and insulin resistance. RESULT(S): There was no significant difference concerning plasma adrenomedullin concentrations between the groups. In patients with PCOS, fasting glucose, fasting insulin, body mass index, and free T were inversely correlated with the plasma adrenomedullin. Plasma adrenomedullin was significantly correlated with glucose:insulin ratio. After controlling for body mass index, there were no significant correlations between the above-mentioned parameters. CONCLUSION(S): Adrenomedullin may play a role in regulating the insulin metabolism in patients with PCOS.

Adolescent↗

PubMed2006

Prenatal growth restraint followed by catch-up of weight: a hyperinsulinemic pathway to polycystic ovary syndrome.

One of the pathways to polycystic ovary syndrome (PCOS) starts with an early-life sequence of prenatal growth restraint followed by catch-up of weight during infancy. This sequence results by mid-childhood in a pre-PCOS state including hyperinsulinemia, a low-grade proinflammatory state, an amplified adrenarche (with or without precocious pubarche), and an adipose body composition even in the absence of obesity. This variant of pre-PCOS and PCOS responds well to intervention with metformin.

Aging↗

PubMed2006

Estrogenic ovulatory dysfunction or functional female hyperandrogenism: an argument to discard the term polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders seen among reproductive-age women, with a prevalence of 4%-9% depending on the criteria used to define the syndrome. The diagnostic criteria for PCOS have been surprisingly controversial and confusing for patients, clinicians, and researchers. We believe that the confusion surrounding PCOS arises almost entirely because its name refers to a trait that is inconsistently present and irrelevant to both the etiology and the treatment of the disorder. We suggest that merely abandoning the term PCOS will cure much of what has ailed us for decades and allow us to focus on the etiology and treatment of the causes of what the experts in this field have come to recognize as functional female hyperandrogenism.

Anovulation↗

PubMedDate not supplied

Evaluation of a new surgical approach for the treatment of clomiphene citrate-resistant infertility in polycystic ovary syndrome: laparoscopic ovarian multi-needle intervention.

Laparoscopic ovarian drilling (LOD) is the accepted second-line treatment for clomiphene citrate-resistant anovulatory infertility in polycystic ovary syndrome (PCOS). Although multiple pregnancy rates are reduced with ovarian drilling procedures, postoperative adhesion formation is a potential complication in up to 85% of the women subjected to laparoscopic destructive ovarian procedures. Our objective was to determine the effectiveness of a new, specially designed laparoscopic device and technique that might enable treatment for patients with anovulatory PCOS with less trauma and fewer postoperative adhesions. Thirty-five infertile clomiphene citrate-resistant women with PCOS were included. Seventeen women underwent laparoscopic ovarian multi-needle intervention (LOMNI), and 18 women received step-up ovulation induction treatment with recombinant follicle-stimulating hormone followed by intrauterine insemination for three cycles. Patients were followed for a period of 6 months after either laparoscopic surgery or the initiation of ovulation induction therapy. Outcome measures were cycle regularity, pregnancy rate, safety, postoperative adhesion formation, and cost effectiveness. There were no significant differences between the two groups in terms of age, body-mass index, duration of infertility, and basal cycle-day 2 hormone levels. Significant improvement in cycle regularity (p <.01) was found after LOMNI. Cumulative pregnancy rates (35.3% in the LOMNI group vs 33.3% in the ovulation induction group) did not differ between the groups. No adverse events following surgery were noted. Moderate ovarian hyperstimulation syndrome and multiple pregnancies occurred in four and two patients, respectively, in the ovulation induction group. Eight nonpregnant women in the LOMNI group underwent repeat laparoscopy at the end of the follow-up period. No adhesion formation attributable to LOMNI was observed in any of those eight women. The cost of LOMNI was significantly (p <.001) lower than the ovulation induction treatment. In conclusion, LOMNI may be a safe, inexpensive, and effective procedure for the treatment of CC-resistant infertility in patients with PCOS. It seems to preserve the beneficial effects and probably omits unwanted effects (such as adhesion formation) of LOD.

Adult↗

PubMed2004

Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome.

OBJECTIVE: Girls with low birth weight (LBW) and with a history of precocious pubarche in childhood (PP) are at high risk of polycystic ovary syndrome (PCOS) in adolescence. In formerly LBW-PP girls, we examined whether initiation of insulin sensitization therapy early after menarche could prevent progression of PCOS features. Study design Twenty-four girls, small at term birth (mean weight, 2.4 kg), who presented with PP (at mean age 6.7 years) and were currently (mean age, 12.4 years) postmenarcheal, with hyperinsulinemic hyperandrogenemia but nonobese, were randomly assigned to receive metformin (850 mg/d) or no treatment for 12 months. Six-month fasting blood samples were collected, and body composition was assessed by dual-energy x-ray absorptiometry. In addition, overnight growth hormone (GH) and gonadotropin secretion was analyzed in 10 girls (6 treated; 4 untreated) at 0 and 6 months. RESULTS: At baseline, compared with healthy control subjects, LBW-PP girls had dyslipidemia, excess truncal fat, reduced lean body mass, and increased insulin-like growth factor-I and GH levels. In untreated girls, insulin sensitivity, serum androgens, lipids, total and truncal fat mass, and lean body mass significantly diverged further from normal over 12 months. In metformin-treated girls, all these abnormalities significantly reversed within 6 months, and body composition continued to improve between 6 and 12 months. CONCLUSIONS: Early metformin therapy prevents progression from PP to PCOS in a high-risk group of formerly LBW girls. This confirms the key role of hyperinsulinemic insulin resistance in the ontogeny of PCOS. Furthermore, normalization of body composition, lipid profiles, and GH secretion could reduce long-term cardiovascular risk.

Adolescent↗

PubMed2005

Idiopathic intracranial hypertension, polycystic-ovary syndrome, and thrombophilia.

We studied thrombophilia, hypofibrinolysis, and polycystic-ovary syndrome (PCOS) in 65 women consecutively referred because of idiopathic intracranial hypertension (IIH) as a means of better understanding the origin of IIH, with the ultimate goal of developing novel medical therapies for IIH. Our hypothesis: IIH results in part from inadequate drainage of cerebrospinal fluid (CSF) resulting from thrombotic obstruction to CSF resorption-outflow, favored by thrombophilia-hypofibrinolysis. We conducted the polymerase chain reaction (PCR) and assessed serologic coagulation measures in 65 women (64 of them white) with IIH, PCR in 102 healthy white female controls (72 children, 30 age-matched adults), and serologic measures in the 30 adults. Of the 65 patients, 37 (57%) were found to have PCOS; 16 (43%) were obese (BMI > or = 30 to < 40), and 19 (51%) were extremely obese (BMI > or = 40). Of the 65 women with IIH, 25 (38%) were homozygous for the thrombophilic C677T MTHFR mutation, compared with 14% of controls (14/102) ( P = .0002). Thrombophilic high concentrations of factor VIII (>150%) were present in 9 of 65 (14%) IIH cases, compared with 0 of 30 controls (0%) (Fisher's p [p f ] = .053). An increased concentration of lipoprotein A (> or = 35 mg/dL), associated with hypofibrinolysis, was present in 19 of 65 IIH cases (29%), compared with 3 of 30 controls (10%) (p f = .039). IIH occurred in 18 of 65 IIH patients taking estrogen-progestin contraceptives (28%), in 6 patients taking hormone-replacement therapy (9%), and in 5 pregnant subjects (8%). We speculate that PCOS, associated with obesity and extreme obesity, is a treatable promoter of IIH. We also speculate that if thrombophilia-hypofibrinolysis and subsequent thrombosis are associated with reduced CSF resorption in the arachnoid villi of the brain, thrombophilia and hypofibrinolysis-often exacerbated by thrombophilic exogenous estrogens, pregnancy, or the paradoxical hyperestrogenemia of PCOS-are treatable promoters of IIH.

Adolescent↗

PubMed1995

The genetics of polycystic ovary syndrome.

Problems that confound the clinical characterization of polycystic ovary syndrome (PCOS) also complicate the search for its genetic cause. There is no consensus as to the nature of the clinical phenotype for PCOS, and there is even doubt whether polycystic ovaries are an indispensable part of the syndrome. Few ethnic studies on PCOS have been performed, although it has been reported in most major racial groups. Genetic studies of family clusters and relatives of affective probands have shown a high incidence of affected relatives. A dominant mode of inheritance, rather than a recessive one, seems more likely. Multiple genetic causes of adult-onset hyperandrogenism and chronic anovulation have been identified. Chromosomal studies of patients with PCOS have shown no consistent abnormality. Molecular genetic studies are now ongoing. Future genetic models should consider such problematic areas as the heterogeneity of the syndrome, phenotypes in males as well as in females in the nonreproductive years, the exclusion of secondary causes of hyperandrogenism, and the persistence of a syndrome that adversely affects fecundity.

Diabetes Mellitus, Type 2↗

PubMed2000

Pregnancies and deliveries after in vitro maturation culture followed by in vitro fertilization and embryo transfer without stimulation in women with polycystic ovary syndrome.

OBJECTIVE: To improve the efficacy of an IVF-ET program for unstimulated patients with polycystic ovary syndrome (PCOS) with the use of culture for oocyte maturation. DESIGN: Prospective studies with the comparison of different ET procedures from March 1995 through February 1998. SETTING: University-affiliated hospital. PATIENT(S): Ninety-four cycles in 64 consenting patients with PCOS. INTERVENTION(S): Immature oocytes were retrieved from unstimulated patients with PCOS and subsequently cultured and fertilized in vitro. Zygote intrafallopian transfer (ZIFT), uterine ET, or a combined approach of ZIFT + uterine ET was subsequently performed. MAIN OUTCOME MEASURE(S): Laboratory and clinical data. RESULT(S): Among 1, 280 immature oocytes (13.6 +/- 7.5 oocytes per patient) retrieved, 89% (1,139) were morphologically normal, and 62.2% (708/1,139) of the normal oocytes matured in vitro after culture for 48 hours. When intracytoplasmic sperm injection was performed, 68% (481/708) developed to the normal pronuclear stage, and 88.1% of the embryos cocultured with Vero cells (266/302) cleaved. Eighty-five ET cycles were conducted and pregnancy was established in 23 cycles (27.1%), which consisted of 8 after uterine ET and 15 after a combined approach. Seventeen patients delivered 20 normal infants. CONCLUSION(S): The IVF-ET method using no ovarian stimulation followed by in vitro maturation culture can be a feasible assisted reproductive technology for treatment of PCOS with various complications.

Adult↗

PubMed2000

Effects of laparoscopic ovarian drilling on serum vascular endothelial growth factor and on insulin responses to the oral glucose tolerance test in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the serum vascular endothelial growth factor concentrations and insulin responses to the oral glucose tolerance test before and after laparoscopic ovarian drilling in women with PCOS. DESIGN: Prospective study. SETTING: University teaching center. PATIENT(S): Twenty-seven women with clomiphene citrate-resistant polycystic ovary syndrome. INTERVENTION(S): Laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): VEGF levels and insulin responses to OGTT before and after ovarian drilling. RESULT(S): No difference was found in VEGF levels in women with PCOS before (6.0 +/- 1.2 ng/mL) and after ovarian drilling (5.5 +/- 1.2 ng/mL). VEGF levels before and after ovarian drilling in women who conceived were, respectively, 5.9 +/- 1.0 and 5.1 +/- 0.9 ng/mL and in those who did not conceive were 6.0 +/- 1.3 and 5.7 +/- 1.2 ng/mL. No correlation was found between baseline serum insulin and VEGF levels. VEGF concentrations in women with normal ovaries (4.5 +/- 1.7 ng/mL) were significantly lower than in women with PCOS. There was no difference in glucose and insulin responses to OGTT before and after ovarian drilling. CONCLUSION(S): VEGF levels in women with PCOS are higher than in normal women, and ovarian drilling does not affect these levels. The procedure does not change insulin responses to OGTT.

Analysis of Variance↗

PubMed2000

Mutation analysis of the growth differentiation factor-9 and -9B genes in patients with premature ovarian failure and polycystic ovary syndrome.

OBJECTIVES: To investigate whether growth differentiation factor (GDF)-9 or GDF-9B/bone morphogenetic protein (BMP)-15 mutation is present in Japanese women with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS). DESIGN: Clinical and molecular studies. SETTING: Outpatient clinic in a university hospital. PATIENT(S): Fifteen women with POF, 38 women with PCOS, and 3 normal fertile controls. INTERVENTION(S): Extraction of DNA from blood samples for subsequent polymerase chain reaction (PCR). MAIN OUTCOME MEASURE(S): Amplified DNA was analyzed by denaturing gradient gel electrophoresis (DGGE) and/or by direct sequencing. RESULT(S): No missense mutation was found in any exons of the GDF-9 gene and the GDF-9B/BMP-15 gene in patients with POF and PCOS. CONCLUSION(S): The missense mutation in the GDF-9 gene or the GDF-9B/BMP-15 gene is uncommon in anovulatory Japanese women with POF and PCOS.

Adult↗

PubMed2001

Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study.

OBJECTIVE: To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome (PCOS). DESIGN: Prospective pilot study. SETTING: Outpatient. PATIENT(S): Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin. INTERVENTION(S): Metformin, 1.5-2.55 g/day, throughout pregnancy. MAIN OUTCOME MEASURE(S): Rates of first-trimester spontaneous abortion and teratogenicity. RESULT(S): Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaneous abortion (10%), and 3 normal ongoing pregnancies (30%) (all > or = 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P<.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9 (47%) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 and one at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04). CONCLUSION(S): Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.

Abnormalities, Drug-Induced↗

PubMed2001

Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome.

OBJECTIVE: To determine whether the known inactivating FSH receptor gene mutations are present in Japanese women with secondary amenorrhea because of premature ovarian failure (POF) and polycystic ovary syndrome (PCOS). DESIGN: Clinical and molecular studies. SETTING: An outpatient clinic in a university hospital. PATIENT(S): Fifteen women with idiopathic POF, 38 women with PCOS, and three normal controls. INTERVENTION(S): Extraction of DNA from blood samples for subsequent polymerase chain reaction (PCR). MAIN OUTCOME MEASURE(S): PCR fragments digested with MunI, BsmI, and HhaI were compared in patients and controls. PCR fragments were also analyzed by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. RESULT(S): No inactivating mutations reported thus far in exons 6, 7, 9, and 10 of the FSH receptor gene were identified in Japanese women with POF and PCOS. DGGE analysis of PCR fragments of exon 10 also revealed no FSH receptor gene mutations in this region. CONCLUSION(S): Although we cannot exclude the presence of point mutations in other regions of the FSH receptor gene, the described FSH receptor mutations may be uncommon in Japanese patients with POF and PCOS.

Adult↗

PubMed2001

Altered autophosphorylation of the insulin receptor in the ovary of a woman with polycystic ovary syndrome.

OBJECTIVE: To determine whether the tyrosine autophosphorylation of the insulin receptor (IR) in the ovary of a woman with polycystic ovary syndrome (PCOS) was reduced compared to normal. DESIGN: Experimental study. SETTING: Tertiary care medical center. PATIENT(S): One woman with PCOS and one healthy control, both of whom underwent a hysterectomy and bilateral salpingo-oophorectomy. INTERVENTION(S): Plasma membrane fraction of ovarian tissue was isolated, and the IR was purified and concentrated. MAIN OUTCOME MEASURE(S): Western blots of the IR, which had been incubated with and without insulin, were prepared. Colorimetric and chemiluminescent methods were used to detect the presence of the IR beta-subunit and IR tyrosine autophosphorylation, respectively. RESULT(S): The presence of the beta-subunit of the IR was identified in both ovarian samples. The degree of insulin-stimulated IR tyrosine autophosphorylation, reflected by the mean (+/-SD) relative optical density of the 95 kd band, was 4.3-fold higher in the normal ovary compared to the PCOS ovary (0.56 +/- 0.18 optical density vs. 0.13 +/- 0.10 optical density, respectively). CONCLUSION(S): Tyrosine autophosphorylation of the IR may be decreased in the ovaries of women with PCOS, similar to the findings in other tissues. The mechanisms through which insulin acts to produce an excess in ovarian androgen production in the face of a decrease in ovarian IR autophosphorylation remain to be determined.

Adult↗

PubMed2001

Dynamics of bioactive follicle-stimulating hormone secretion in women with polycystic ovary syndrome: effects of estradiol and progesterone.

OBJECTIVE: To determine the nature of bioactive FSH secretion in anovulatory women with polycystic ovary syndrome (PCOS) and its modulation by luteal levels of E2 and P. DESIGN: Interventional and observational study. SETTING: Academic clinical research center. PATIENT(S): Five patients with PCOS. INTERVENTION(S): Treatment for 21 days with luteal levels of E2 and P. MAIN OUTCOME MEASURES: Serum levels of immunoreactive LH, immunoreactive FSH, bioreactive FSH, and the FSH isoform distribution pattern. Blood was sampled frequently and GnRH testing was done on day 0 (before treatment), days 10 and 20 (during treatment), and day 28 (7 days after treatment). RESULT(S): Treatment with E2 and P suppressed circulating immunoreactive LH and immunoreactive FSH but not bioreactive FSH. Anovulatory women with PCOS showed a predominantly acidic pattern of FSH isoform distribution. Treatment with E2 and P shifted the distribution profile of FSH isoforms to the less acidic. After cessation of E2-P treatment, FSH reverted to its pretreatment pattern of distribution. CONCLUSION(S): Resumption of follicular growth after luteal replacement of E2 and P in anovulatory women with PCOS may be related to the reduction in the elevated LH/FSH ratio and accompanying changes in the FSH signal.

Androstenedione↗

PubMed2001

Role of the follistatin gene in women with polycystic ovary syndrome.

OBJECTIVE: To search for mutations in the coding exons of the follistatin gene of women diagnosed with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Tertiary institutional hospital. PATIENT(S): Thirty-four women diagnosed with PCOS and 15 healthy control women. INTERVENTION(S): Whole blood and serum samples were collected during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Circulating total testosterone (T), sex hormone-binding globulin (SHBG), calculated free T (FT), androstenedione (A), dehydroepiandrosterone-sulfate (DHEAS), LH, FSH, E2, and basal and adenocorticotropic hormone (ACTH)-stimulated 17-hydroxyprogesterone (17-OHP) were determined. Insulin resistance was estimated from fasting glucose and insulin levels, using the homeostasis model assessment. The coding regions of the follistatin gene were studied by heteroduplex analysis after polymerase chain reaction amplification. RESULT(S): Women with PCOS presented with higher body-mass index, insulin resistance, T, FT, A, and ACTH-stimulated 17-OHP serum concentrations and lower SHBG serum levels, as compared with controls. No differences were observed among the groups in serum DHEAS, basal 17-OHP, E(2), LH, and FSH. No mutations were found in coding regions of the follistatin gene, with the exception of a G to A change at cDNA position 951, resulting in a silent mutation. This change was present in 2 (5.9%) of 34 patients and 1 (6.7%) of 15 controls. CONCLUSION(S): Mutations in the coding regions of the follistatin gene do not appear to be related to PCOS.

17-alpha-Hydroxyprogesterone↗

PubMed2001

A new ultrasound criterion for the diagnosis of polycystic ovary syndrome: the ovarian stroma/total area ratio.

OBJECTIVE: To evaluate whether some ultrasound parameters of ovarian morphology can discriminate between control women and patients with polycystic ovary syndrome (PCOS). DESIGN: Retrospective data analysis. SETTING: Volunteers women in an academic research environment. PATIENT(S): Eighty amenorrheic or oligomenorrheic women and 30 normal ovulatory control participants. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We evaluated ovarian volume, area, stroma, and the stroma/total area (S/A) ratio by use of transvaginal pelvic ultrasound; and we assayed serum levels of gonadotropin, androgen, and estradiol during the early follicular phase (days 2 to 5) of the menstrual cycle in regularly cycling controls and on a random day in amenorrheic patients. RESULT(S): Patients with PCOS showed significantly higher ovarian volume, area, stroma, and mean S/A ratio when compared to multifollicular and control groups. Cut-off values have been defined for ovarian volume (13.21 mL), area (7.00 cm2), stroma (1.95 cm2), and S/A ratio (0.34). The sensitivity for PCOS diagnosis was 21%, 4%, 62%, and 100%, respectively. The S/A ratio showed the most significant correlation with the androgen levels. CONCLUSION(S): The evaluation of the S/A ratio can differentiate between PCOS and control or multifollicular women with both a sensitivity and a specificity of 100%. Furthermore, this ultrasound parameter is strictly related to hormonal milieu and to anthropometric characteristics.

17-alpha-Hydroxyprogesterone↗